tbuckley/cabot-search huggingface dataset:
Single-cell profiling of GP2-enriched pancreatic progenitors to simultaneously create acinar, ductal, and endocrine organoids
Authors: Sarah Merz, Markus Breunig, Michael Karl Melzer, Sandra Heller, Sandra Wiedenmann, Thomas Seufferlein, Matthias Meier, Jana Krüger, Medhanie A Mulaw, Meike Hohwieler, Alexander Kleger
Journal: Theranostics (2023)

Rationale: Pancreatic lineage specification follows the formation of tripotent pancreatic progenitors (PPs). Current protocols rebuilding PPs in vitro have an endocrine lineage bias and are mostly based on PDX1/NKX6-1 coexpression neglecting other markers decisive for PP heterogeneity and lineage potential. However, true tripotent PPs are of utmost interest to study also exocrine disorders such as pancreatic cancer and to simultaneously generate all three pancreatic lineages from the same ancestor. Methods: Here, we performed a comprehensive compound testing to advance the generation of multipotent progenitors, which were further characterized for their trilineage potential in vitro and in vivo. The heterogeneity and cell-cell communication across the PP subpopulations were analyzed via single-cell transcriptomics. Results: We introduce a novel PP differentiation platform based on a comprehensive compound screening with an advanced design of experiments computing tool to reduce impurities and to increase Glycoprotein-2 expression and subsequent trilineage potential. Superior PP tripotency was proven in vitro by the generation of acinar, endocrine, and ductal cells as well as in vivo upon orthotopic transplantation revealing all three lineages at fetal maturation level. GP2 expression levels at PP stage ascribed varying pancreatic lineage potential. Intermediate and high GP2 levels were superior in generating endocrine and duct-like organoids (PDLO). FACS-based purification of the GP2high PPs allowed the generation of pancreatic acinar-like organoids (PALO) with proper morphology and expression of digestive enzymes. scRNA-seq confirmed multipotent identity, positioned the GP2/PDX1/NKX6-1high population next to human fetal tip and trunk progenitors and identified novel ligand-receptor (LR) interactions in distinct PP subpopulations. LR validation experiments licensed midkine and VEGF signaling to increase markers labelling the single cell clusters with high GP2 expression. Conclusion: In this study, we guide human pluripotent stem cells into multipotent pancreatic progenitors. This common precursor population, which has the ability to mature into acinar, ductal and functional β-cells, serves as a basis for studying developmental processes and deciphering early cancer formation in a cell type-specific context. Using single-cell RNA sequencing and subsequent validation studies, we were able to dissect PP heterogeneity and specific cell-cell communication signals.
Repopulated retinal microglia promote Müller glia reprogramming and preserve visual function in retinal degenerative mice
Authors: Xuan Cheng, Hui Gao, Zui Tao, Zhiyuan Yin, Zhe Cha, Xiaona Huang, Yikui Zhang, Yuxiao Zeng, Juncai He, Lingling Ge, Luodan A, Haiwei Xu, Guang-Hua Peng
Journal: Theranostics (2023)

Rationale: Müller glia (MG) play a key role in maintaining homeostasis of the retinal microenvironment.In zebrafish, MG reprogram into retinal progenitors and repair the injured retina, while this MG regenerative capability is suppressed in mammals.It has been revealed that microglia in zebrafish contribute to MG reprogramming, whereas those in mammals are over-activated during retinal injury or degeneration, causing chronic inflammation, acceleration of photoreceptor apoptosis, and gliosis of MG.Therefore, how to modulate the phenotype of microglia to enhance MG reprogramming rather than gliosis is critical.Methods: PLX3397, a colony-stimulating factor 1 receptor inhibitor, was applied to deplete microglia in the retinas of retinal degeneration 10 (rd10) mice, and withdrawal of PLX3397 was used to induce the repopulated microglia (Rep-MiG).The protective roles of the Rep-MiG on the degenerative retina were assessed using a light/dark transition test, and scotopic electroretinogram recordings.Immunofluorescence, western blot, transcriptomic sequencing, and bioinformatics analysis were performed to investigate the effects and mechanisms of microglia on MG reprogramming.Results: Following PLX3397 withdrawal, Rep-MiG replenished the entire retina with a ramified morphology and significantly improved the retinal outer nuclear layer structure, the electroretinography response, and the visual behavior of rd10 mice.Coincidentally, MG were activated, de-differentiated, and showed properties of retina progenitors in a spatial correlation with Rep-MiG.Morphological and transcriptomic analyses revealed Rep-MiG significantly enhanced protease inhibitor activity and suppressed extracellular matrix (ECM) levels during retinal degeneration.Conclusions: It suggested that Rep-MiG with the homeostasis characteristic stimulated the progenitor cell-like properties of MG, probably through regulating ECM remodeling, which protected photoreceptors and improved visual function of rd10 mice.It might be a potential protocol to reprogram MG and delay mammal retinal degeneration.
Prediabetes Diagnosis and Management
Authors: William H. Herman
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Opioid Prescribing and Suicide Risk in the United States
Authors: Mark Olfson, Timothy Waidmann, Marissa King, Vincent Pancini, Michael Schoenbaum
Journal: American Journal of Psychiatry (2023)

This study estimates associations of regional change in opioid prescribing with total suicide deaths and suicide overdose deaths involving opioids.A panel analysis was performed with 2009-2017 U.S. national IQVIA Longitudinal Prescription Database data and National Center for Health Statistics mortality data aggregated into commuting zones (N=886), which together span the United States. Opioid prescription exposures included opioid prescriptions per capita and percentages of patients with any opioid prescription, with high-dose prescriptions (>120 mg of morphine equivalents), with long-term prescriptions (≥60 consecutive days), and with prescriptions from three or more prescribers. Linear regression models were used with year and commuting zone fixed effects.Suicide deaths were significantly positively associated with opioid prescriptions per capita (β=0.045), having any opioid prescription (β=0.069), having high-dose prescriptions (β=0.024), having long-term prescriptions (β=0.028), and having three or more opioid prescribers (β=0.046). Similar significant associations were observed between each of the five opioid prescription measures and suicide overdose deaths involving opioids (β range, 0.029-0.042). However, opioid prescriptions per capita, having any opioid prescription, and having three or more opioid prescribers were each negatively associated with unintentional opioid-related deaths in people in the 10- to 24-year and 25- to 44-year age groups.In this retrospective study of U.S. commuting zone-level opioid prescriptions and mortality, regional decreases in opioid prescriptions were consistently associated with declines in total suicide deaths, including suicide overdose deaths involving opioids. For some opioid prescribing measures, negative associations were observed with unintentional overdose deaths involving opioids among younger people. Individual-level inferences are limited by the ecological nature of the analysis.
Combination of AFP vaccine and immune checkpoint inhibitors slows hepatocellular carcinoma progression in preclinical models
Authors: Xinjun Lu, Shanshan Deng, Jiejie Xu, Benjamin L. Green, Honghua Zhang, Guofei Cui, Yi Zhou, Yi Zhang, Hongwei Xu, Fapeng Zhang, Rui Mao, Sheng Zhong, Thorsten Cramer, Matthias Evert, Diego F. Calvisi, Yukai He, Chao Liu, Xin Chen
Journal: Journal of Clinical Investigation (2023)

Many patients with hepatocellular carcinoma (HCC) do not respond to the first-line immune checkpoint inhibitor treatment. Immunization with effective cancer vaccines is an attractive alternative approach to immunotherapy. However, its efficacy remains insufficiently evaluated in preclinical studies. Here, we investigated HCC-associated self/tumor antigen, α-fetoprotein-based (AFP-based) vaccine immunization for treating AFP (+) HCC mouse models. We found that AFP immunization effectively induced AFP-specific CD8+ T cells in vivo. However, these CD8+ T cells expressed exhaustion markers, including PD1, LAG3, and Tim3. Furthermore, the AFP vaccine effectively prevented c-MYC/Mcl1 HCC initiation when administered before tumor formation, while it was ineffective against full-blown c-MYC/Mcl1 tumors. Similarly, anti-PD1 and anti-PD-L1 monotherapy showed no efficacy in this murine HCC model. In striking contrast, AFP immunization combined with anti-PD-L1 treatment triggered significant inhibition of HCC progression in most liver tumor nodules, while in combination with anti-PD1, it induced slower tumor progression. Mechanistically, we demonstrated that HCC-intrinsic PD-L1 expression was the primary target of anti-PD-L1 in this combination therapy. Notably, the combination therapy had a similar therapeutic effect in the cMet/β-catenin mouse HCC model. These findings suggest that combining the AFP vaccine and immune checkpoint inhibitors may be effective for AFP (+) HCC treatment.
Molecular profiling and treatment pattern differences between intrahepatic and extrahepatic cholangiocarcinoma
Authors: Kristen Spencer, Leontios Pappas, Islam Baiev, Jordan Maurer, Andrea Grace Bocobo, Karen Zhang, Apurva Jain, Anaemy Danner De Armas, Stephanie Reyes, Tri Minh Le, Osama E Rahma, Jennifer Stanton, Thomas T DeLeon, Marc Roth, Mary Linton B Peters, Andrew X Zhu, Jochen K Lennerz, A John Iafrate, Kylie Boyhen, Christine VanCott, Lewis R Roberts, Stacie Lindsey, Nora Horick, Laura Williams Goff, Kabir Mody, Mitesh J Borad, Rachna T Shroff, Robin Kate Kelley, Milind M Javle, Lipika Goyal
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Background Treatment patterns for intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) differ, but limited studies exist comparing them. This study examines differences in molecular profiling rates and treatment patterns in these populations, focusing on use of adjuvant, liver-directed, targeted, and investigational therapies. Methods This multicenter collaboration included patients with ICC or ECC treated at 1 of 8 participating institutions. Retrospective data were collected on risk factors, pathology, treatments, and survival. Comparative statistical tests were 2-sided. Results Among 1039 patients screened, 847 patients met eligibility (ICC = 611, ECC = 236). Patients with ECC were more likely than those with ICC to present with early stage disease (53.8% vs 28.0%), undergo surgical resection (55.1% vs 29.8%), and receive adjuvant chemoradiation (36.5% vs 4.2%) (all P &amp;lt; .00001). However, they were less likely to undergo molecular profiling (50.3% vs 64.3%) or receive liver-directed therapy (17.9% vs 35.7%), targeted therapy (4.7% vs 18.9%), and clinical trial therapy (10.6% vs 24.8%) (all P &amp;lt; .001). In patients with recurrent ECC after surgery, the molecular profiling rate was 64.5%. Patients with advanced ECC had a shorter median overall survival than those with advanced ICC (11.8 vs 15.1 months; P &amp;lt; .001). Conclusions Patients with advanced ECC have low rates of molecular profiling, possibly in part because of insufficient tissue. They also have low rates of targeted therapy use and clinical trial enrollment. While these rates are higher in advanced ICC, the prognosis for both subtypes of cholangiocarcinoma remains poor, and a pressing need exists for new effective targeted therapies and broader access to clinical trials.
Variation in DNA Methylation in Avian Nestlings Is Largely Determined by Genetic Effects
Authors: Bernice Sepers, Rebecca Shuhua Chen, Michelle Memelink, Koen J F Verhoeven, Kees van Oers
Journal: Molecular Biology and Evolution (2023)

Abstract As environmental fluctuations are becoming more common, organisms need to rapidly adapt to anthropogenic, climatic, and ecological changes. Epigenetic modifications and DNA methylation in particular provide organisms with a mechanism to shape their phenotypic responses during development. Studies suggest that environmentally induced DNA methylation might allow for adaptive phenotypic plasticity that could last throughout an organism's lifetime. Despite a number of studies demonstrating environmentally induced DNA methylation changes, we know relatively little about what proportion of the epigenome is affected by environmental factors, rather than being a consequence of genetic variation. In the current study, we use a partial cross-foster design in a natural great tit (Parus major) population to disentangle the effects of common origin from common rearing environment on DNA methylation. We found that variance in DNA methylation in 8,315 CpG sites was explained by a common origin and only in 101 by a common rearing environment. Subsequently, we mapped quantitative trait loci for the brood of origin CpG sites and detected 754 cis and 4,202 trans methylation quantitative trait loci, involving 24% of the CpG sites. Our results indicate that the scope for environmentally induced methylation marks independent of the genotype is limited and that the majority of variation in DNA methylation early in life is determined by genetic factors instead. These findings suggest that there may be little opportunity for selection to act on variation in DNA methylation. This implies that most DNA methylation variation likely does not evolve independently of genomic changes.
Changes in In-Person, Audio-Only, and Video Visits in California’s Federally Qualified Health Centers, 2019-2022
Authors: Lori Uscher-Pines, Colleen M. McCullough, Jessica L. Sousa, Sarita D. Lee, Allison J. Ober, Diana Camacho, Kandice A. Kapinos
Journal: JAMA (2023)

This study assesses telehealth visit trends among California federally qualified health centers from 2019 to 2022.
HDACIs and TKIs combinations and their liposomal delivery for cancer treatment
Authors: Cindy Schelker, Patrycja Nowak-Sliwinska, Gerrit Borchard
Journal: Journal of Controlled Release (2023)

Fixed-drug combinations have been used for the treatment of cancer. Current anticancer therapies, however, tend to induce resistance and provoke important toxicity. Therefore, there is still a need for further optimized treatments that would also take into account drug-drug interactions. Tyrosine kinase inhibitors (TKIs) and Histone deacetylase inhibitors (HDACIs) are two anticancer drug classes currently used separately in clinical practice. Those drug classes are currently being investigated in clinical trials. Several findings confirm the safety and tolerability of these treatments accompanied by clinical improvement. The activity and specificity of drug combinations can be further improved by employing appropriate drug delivery systems, such as nanocarrier systems. The different pharmacokinetic profiles of each drug may lead to a loss in synergistic effects, affecting treatment efficiency. Several combinations of either TKI or HDACI with an anticancer drug of another class co-loaded inside liposomal carriers are being investigated in vivo and show promising results in terms of efficacy and safety. In this review we discuss strategies for the delivery of synergistic drug combinations for cancer treatment.
Malignancy risk in atopic dermatitis: heterogenous effects and perspectives
Authors: Ida Vittrup
Journal: British Journal of Dermatology (2023)

Journal Article Malignancy risk in atopic dermatitis: heterogenous effects and perspectives Get access Ida Vittrup Ida Vittrup Department of Dermatology, Copenhagen University Hospital – Bispebjerg and Frederiksberg, Copenhagen, Denmark Correspondence: Ida Vittrup. Email: ida.vittrup.nielsen.01@regionh.dk https://orcid.org/0000-0002-3192-6135 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 189, Issue 1, July 2023, Pages 4–5, https://doi.org/10.1093/bjd/ljad119 Published: 11 April 2023 Article history Received: 03 April 2023 Published: 11 April 2023 Accepted: 03 May 2023 Corrected and typeset: 26 May 2023
Inverse agonists of retinoic acid receptor/retinoid X receptor signaling as lineage-specific antitumor agents against human adenoid cystic carcinoma
Authors: Sara Viragova, Luis Aparicio, Pierangela Palmerini, Junfei Zhao, Luis E Valencia Salazar, Alexandra Schurer, Anika Dhuri, Debashis Sahoo, Christopher A Moskaluk, Raul Rabadan, Piero Dalerba
Journal: JNCI Journal of the National Cancer Institute (2023)

Adenoid cystic carcinoma (ACC) is a lethal malignancy of exocrine glands, characterized by the coexistence within tumor tissues of 2 distinct populations of cancer cells, phenotypically similar to the myoepithelial and ductal lineages of normal salivary epithelia. The developmental relationship linking these 2 cell types, and their differential vulnerability to antitumor treatments, remains unknown.
Evictions and Infant and Child Health Outcomes
Authors: Bruce Ramphal, Ryan Keen, Sakurako S. Okuzuno, Dennis Ojogho, Natalie Slopen
Journal: JAMA Network Open (2023)

Millions of rental evictions occur in the United States each year, disproportionately affecting households with children. Increasing attention has been paid to the impact of evictions on child health outcomes.
Hydrogen Sulfide Gas Amplified ROS Cascade: FeS@GOx Hybrid Nanozyme Designed for Boosting Tumor Chemodynamic Immunotherapy
Authors: Wanying Sun, Chengyuan Zhu, Juan Song, Shi‐Chen Ji, Bang‐Ping Jiang, Hong Liang, Xing‐Can Shen
Journal: Advanced Healthcare Materials (2023)

Chemodynamic immunotherapy that utilizes catalysts to produce reactive oxygen species (ROS) for killing tumor cells and arousing antitumor immunity has received considerable attention. However, it is still restricted by low ROS production efficiency and insufficient immune activation, due to intricate redox homeostasis in the tumor microenvironment (TME). Herein, a metalloprotein-like hybrid nanozyme (FeS@GOx) is designed by in situ growth of nanozyme (ferrous sulfide, FeS) in a natural enzyme (glucose oxidase, GOx) to amplify ROS cascade for boosting chemodynamic immunotherapy. In FeS@GOx, GOx allows the conversion of endogenous glucose to gluconic acid and hydrogen peroxide, which provides favorable increasing hydrogen peroxide for subsequent Fenton reaction of FeS nanozymes, thus reinforcing ROS production. Notably, hydrogen sulfide (H2 S) release is activated by the gluconic acid generation-related pH decrease, which can suppress the activity of endogenous thioredoxin reductase and catalase to further inhibit ROS elimination. Thus, FeS@GOx can sustainably amplify ROS accumulation and perturb intracellular redox homeostasis to improve chemodynamic therapy and trigger robust immunogenic cell death for effective immunotherapy combined with immune checkpoint blockade. This work proposes a feasible H2 S amplified ROS cascade strategy employing a bioinspired hybrid nanozyme, providing a novel pathway to multi-enzyme-mediated TME modulation for precise and efficient chemodynamic immunotherapy.
Sensitivity of Schizophrenia Endophenotype Biomarkers to Anticholinergic Medication Burden
Authors: Yash B. Joshi, Juan L. Molina, David L. Braff, Michael F. Green, Ruben C. Gur, Raquel E. Gur, Keith H. Nuechterlein, William S. Stone, Tiffany A. Greenwood, Laura C. Lazzeroni, Allen D. Radant, Jeremy M. Silverman, Joyce Sprock, Catherine A. Sugar, Debby W. Tsuang, Ming T. Tsuang, Bruce I. Turetsky, Neal R. Swerdlow, Gregory A. Light
Journal: American Journal of Psychiatry (2023)
it was
Authors: Camille Gwen Rogine
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Over-the-counter Hearing Aids
Authors: Lucas A. Berenbrok, Elaine Mormer
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal